Cellular contraction associated with proliferative retinopathies can ultimately cause retinal folding and detachment. These changes can be reversed by surgery, but the rate of recurrence is high. In some cases this ultimately causes loss of vision. Cellular contraction will ultimately be described in molecular terms and controlled with therapeutic agents. Using an in vitro assay of cellular contraction we propose to focus on the contractile activities of Muller's cells, whose involvement in proliferative vitreoretinopathy is strongly implied by earlier studies. The first phase of this proposal outlines a study in which the effects of known bioactive peptides on Muller's cell contraction will be determined. This will enable us to identify the active species in serum, secreted by endothelial cells and retinal pigment epithelial cells which are each thought to be involved in proliferative disorders. This will also enable us to determine the existence of unknown bioactive peptides in these relevant sources. The relevance of these studies will ultimately be confirmed in a survey of the contraction-promoting potential of normal and pathologic human vitreous. We will ultimately determine the correlation between the levels and species of bioactive peptides with disease state. Two mechanistic studies of Muller's cell contraction will identify the cytoplasmic second messenger involved in propagating contractile signals and identify the cell surface receptors involved in propagating the contractile forces generated by the cytoskeleton. These three studies could yield information which would enable three approaches to preventing cell-mediated retinal detachment by 1) neutralizing targeted contraction-promoting factors, 2) inhibiting cytoplasmic second messengers, and 3) blocking integrin receptors involved in propagating contractile force.